Most viral load blips are short-lasting and of no significance

Michael Carter

Published: 19 May 2008

Approximately a quarter of patients taking anti-HIV treatment have occasional “blips” in their viral load, according to a Dutch study published in the May 1st edition of the Journal of Acquired Immune Deficiency Syndromes. But, provided that viral load quickly returns to undetectable and these blips involve only small increases in viral load, they are not associated with an increased risk of HIV-related illness, a fall in CD4 cell count, or a change in anti-HIV treatment. However, larger and more sustained increases in viral load are often associated with either drug resistance, illness or a change in anti-HIV treatment.

The investigators suggest that leaving treatment unaltered is a perfectly acceptable response to short-lived and low-level viral load blips.

The aim of anti-HIV treatment is to lower the amount of HIV in the blood to undetectable levels (below at least 50 copies/ml). Sustained increases in viral load to detectable levels during anti-HIV treatment can lead to the development of drug resistant virus, a fall in CD4 cell count, and an increased risk of HIV-related illness.

But many people whose viral load falls to undetectable levels have occasional viral load measurements which show that low levels of HIV are detectable in their blood before their viral load quickly becomes undetectable again. These are often called “blips.”

Investigators from the large Dutch ATHENA cohort of antiretroviral-treated patients wanted to try and determine the consequences of low-level and short-lived viral load blips, and larger increases in viral load that last for longer.

They therefore conducted an analysis that included 4447 patients who started anti-HIV treatment for the first time with a combination of potent anti-HIV drugs. These patients all achieved an undetectable viral load after starting anti-HIV treatment in at least two consecutive tests. The researchers wanted to see how many had a subsequent increase in their viral load to detectable levels, at what level, and for how long, and if this involved any subsequent HIV-related illness, changes in anti-HIV treatment, or emergence of drug-resistant virus.

Most of the patients were men (77%), and originated from the Netherlands or another western European country (65%). The majority of individuals were infected with HIV through sex with another man (53%). Median CD4 cell count when viral load was first suppressed to undetectable levels for a sustained period was 390 cells/mm3, and the patients' median age was 39 years.

An undetectable viral load was maintained by 71% of the patients. But 29% of patients (1281 individuals) had at least one viral load blip. In most of these patients viral load during these blips was low, but in 369 patients (5%) it was 1,000 copies/ml or more.

There was no difference in median CD4 cell count between times when viral load was undetectable and during episodes of low-level viral load blips (460 cells/mm3 vs. 480 cells/mm3). But median CD4 cell count was significantly lower in patients with increases in their viral load to above 1,000 copies/ml (360 cells/mm3, p < 0.001). The researchers calculated that CD4 cell count changes during higher-level increases in viral load would have resulted in an average drop in CD4 cell count of 87 cells/mm3 per year.

In most cases (82%), viral load increased to detectable levels in just a single test, before becoming undetectable, or became undetectable in the next test but one (12%). But in 6% of patients the increase in viral load was longer-lasting.

The majority of blips (80%) did not involve any change of treatment, illness, or resistance. However, when the investigators looked at this more closely, they found that the majority of patients (59%) who experienced an increase in their viral load to over 1,000 copies/ml had at least one of these events.

Treatment was changed in 14% of patients with a low-level viral load blip, but in 52% of patients with increases in viral load above 1,000 copies/ml. Similarly, only 2% of patients with low-level blips experienced any sort of HIV-associated illness compared to 30% of those with larger increases in viral load, and resistance was found in only 1% of those with a low viral load blip compared to 23% of those with larger increases in viral load.

Viral load blips are not random events, the investigators suggest, rather they are “partially explained by host-related factors” and that “patients have different tendencies to show blips.”

They note that the probability of low-level viral load blips decreased over the years, and suggest that this is because anti-HIV treatment has “become more potent and easier to adhere to…yielding a more complete and more sustained suppression in viral load.” However, there was no significant change over time in the proportion of patients experiencing large increases in viral load. They therefore write, “this suggests that the mechanism underlying high-level and low-level viraemia is different and that high-level viraemia is most likely the result of true therapy failure or incomplete adherence.”

A higher proportion of viral load blips occurred in winter than summer. They suggest that the reason could be because illness like colds and influenza are more common in the winter months.

They conclude, “short-lasting episodes of low-level viraemia are relatively frequent, and host related and seasonal factors are associated with the occurrence of viraemia. High level viraemia seems to be frequently associated with resistance and often leads to therapy changes.” They add that “leaving therapy unchanged during low-level viraemia is a clinically acceptable strategy.”

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

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checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member
of your healthcare team for advice tailored to your situation.